Summary of work: Alzheimer's disease (AD) is the most widespread among several neurological degenerative diseases (dementias) which occur principally at later ages, occasionally before 60, but more frequently after age 70. This study examines prospective psychological, neurological, and neuropsychological changes in participants from the Baltimore Longitudinal Study of Aging (BLSA). Neurological and neuropsychological examinations are administered to participants aged 60 and older, repeating many of the tests that were administered to these subjects at earlier ages. Diagnoses of probable Alzheimer's disease follow the NINCDS-ADRDA criteria. Estrogen replacement therapy (ERT) was examined as a risk for AD. Approximately 48% of the women in the cohort had used ERT; 34 incident cases of AD were diagnosed during follow-up, including 9 estrogen users. After adjusting for education, the relative risk for AD in ERT users compared to non-users was 0.46 (95% CI=0.209-0.997), indicating a reduced risk of AD for women who had reported the use of estrogen. In addition, ERT may protect against memory decline in nondemented postmenopausal women. These finding support the beneficial role of estrogen on cognitive functioning in aging women. Apolipoprotein E (APOE) genotyping was completed on approximately two-thirds of the active BLSA cohort. Analyses of neuropsychological data on subjects with no evidence of dementia show that subjects with at least one E4 allele show small but consistent declines over six years on mental status and category fluency tests.